One of the goals of auditory neuroscience is to understand how speech and other natural sounds are analyzed and encoded in the human auditory cortex. One major finding is that perception and speech processing are crucially affected by temporal modulations in the acoustic signal. However, identifying in humans the physiological mechanisms that underlie the analysis of perceptually-relevant temporal modulations presents a considerable technical challenge. Extracellular recording methods are ideal for the investigation of time-based neural coding mechanisms, but they are typically limited to a single auditory area and cannot be generally used in human subjects. Magnetoencephalography (MEG) is a non-invasive tool, suitable for use in humans that records high-speed neural signals from the entire brain, though at the cost of significantly coarser spatial resolution. Fortunately, recent work has shown that investigations of the neural coding of acoustic modulations can indeed be conducted using MEG with human subjects. Thus MEG and extracellular recording can both be employed, in complementary ways, to investigate how temporal modulations are encoded by auditory cortex. The goal of this proposed research program is to understand how these acoustic modulations, the building blocks of speech and other natural sounds are encoded in auditory cortex. The acoustic modulations whose encoding is investigated are either embedded in a noisy background, as in a natural auditory scene, or modulated in both frequency and amplitude, independently and simultaneously, as in speech. The research program employs parallel sets of experiments: one set using MEG to record from human auditory cortex, and the other using extracellular recording methods in an animal model. With recordings from individual neurons, from the extracellular local field potential, and from the whole cortex, it may be possible to unify the different schemes used to neurally encode acoustic modulations, up and down the neural hierarchy. PUBLIC HEALTH RELEVANCE: Recent research suggests that a variety of hearing and cognitive impairments result from problems in temporal processing of sounds (e.g. developmental language disorders, and hearing impairment due to aging, auditory neuropathy, or cochlear implants). The present work will provide novel experimental approaches, as well as a rich empirical database on cortical temporal processing in normal human subjects, that can then be used in clinical settings.